We have previously demonstrated that the sphincter of Oddi (SO) plays a major role in controlling bile flow into the duodenum. The overall goal of this proposal is to utilize intracellular and extracellular recording techniques in the opossum to further define myoelectric control activity of the SO. Specific aims of this proposal are to determine the relationship between SO myoelectric activity and intraluminal pressure and propulsion; to study the relationship between gallbladder (GB) or duodenal (D) pressure and SO myoelectric activity; to characterize SO intracellular myoelectric activity and its reaction to enteric peptides; to study the coordination of gastric and GB emptying, and myoelectric activity of the SO; and to create a mathematical model of the myoelectric cycling of the SO. in vivo studies will be carried out in conscious opossums chronically prepared with bipolar electrodes secured to the SO, gastric antrum (GA) and D. Noninvasive radioisotopic techniques with gamma camera scanning will be used to assess simultaneous gastric emptying, bile flow and SO, GA and D myoelectric activity. Recordings will be statistically analyzed and mathematically modeled utilizing computer-directed curvilinear regression. These tests will be repeated after cholecystectomy. Acute in vivo preparations with cannulation of isolated GB and D and electrodes secured to the SO will be used to asses the relationship between graded changes in GB, D pressure and SO myoelectric activity. Whole organ in vitro studies will be carried out in a tissue bath. Bipolar electrodes will be implanted along the SO. A catheter in continuity with a volumetric reservoir and pressure transducer will be secured to both ends of the sphincter and the relationship between myoelectric activity and intraluminal flow determined. Circumferential 2mm sections of SO will be pinned to the floor of a tissue bath and intracellular microelectrode techniques used to record electrical potentials while a force transducer is used to simultaneously monitor mechanical activity. The effect of enteric peptides on intracellular myoelectric and motor activity will be studied. In summary, fundamental control mechanisms of biliary motility will be determined, and the relationship between the SO, GA, D, and GB in determining bile flow elucidated. Studies of the physiology of the SO in concert with the rest of the upper gastrointestinal tract, using techniques available and well-established in our laboratory, will likely unravel many of the unanswered questions of an anatomic region so frequently involved in clinical disorders.